Non-invasive myocardial work in aortic stenosis: validation and improvement in left ventricular pressure estimation.

AIMS: The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS. METHODS AND RESULTS: We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure-strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP. CONCLUSION: This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.

Forest composition change and biophysical climate feedbacks across boreal North America.

Deciduous tree cover is expected to increase in North American boreal forests with climate warming and wildfire. This shift in composition has the potential to generate biophysical cooling via increased land surface albedo. Here we use Landsat-derived maps of continuous tree canopy cover and deciduous fractional composition to assess albedo change over recent decades. We find, on average, a small net decrease in deciduous fraction from 2000 to 2015 across boreal North America and from 1992 to 2015 across Canada, despite extensive fire disturbance that locally increased deciduous vegetation. We further find near-neutral net biophysical change in radiative forcing associated with albedo when aggregated across the domain. Thus, while there have been widespread changes in forest composition over the past several decades, the net changes in composition and associated post-fire radiative forcing have not induced systematic negative feedbacks to climate warming over the spatial and temporal scope of our study.

Reduced exercise capacity is associated with left ventricular systolic dysfunction in long-term survivors of allogeneic hematopoietic stem-cell transplantation.

PURPOSE: Exercise intolerance is a common complication in survivors of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to determine if cardiac function measured with echocardiography is associated with exercise capacity measured with cardio-pulmonary exercise tests in long-term survivors treated in their youth with allo-HSCT. METHODS: The study included 96 patients, of which 54.2% were female, aged 34.9 ± 11.6 years and 17.7 ± 9.3 years after allo-HSCT. Reduced exercise capacity was defined as <85% of predicted-peak oxygen uptake (VO2peak ). Linear regression was used in the prediction of VO2peak (ml/kg/min). Receiver operating characteristic evaluated the accuracy of predicting reduced exercise capacity. RESULTS: VO2peak was 36.2 ± 7.7 ml/kg/min and 43 (44.8%) had reduced exercise capacity. Left ventricular ejection fraction was 55.4 ± 5.9% and global longitudinal strain (GLS) was -17.6% ± 2.0%. Left and right ventricular functions were significantly lower in survivors with reduced exercise capacity. Increased body mass index, lower physical activity score, reduced pulmonary function (by forced expiratory volume in 1-s) and reduced left ventricular systolic function (by GLS) were significant independent predictors for reduced VO2peak . GLS was superior to other echocardiographical indices for identifying reduced exercise capacity (area under curve = 0.64, p = 0.014). CONCLUSIONS: Left ventricular systolic dysfunction measured by GLS is associated with reduced exercise capacity in long-term allo-HSCT survivors.

Graft-Versus-Host-Disease and Health-Related Quality of Life in Young Long-term Survivors of Cancer and Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment predominantly for malignancies. Chronic graft-versus-host disease (cGVHD) is the leading long-term complication after allo-HSCT, but knowledge on cGVHD and health-related quality of life (HRQOL) in long-term survivors of allo-HSCT performed in childhood, adolescence, and young adulthood (CAYA) is scarce. Therefore, we aimed to (1) assess prevalence and risk factors of active cGVHD using the 2014 National Institutes of Health-Consensus criteria, (2) investigate associations between cGVHD severity, patient-reported symptom burden, and HRQOL, and (3) compare HRQOL of survivors to population norms. Methods: We conducted a nationwide cross-sectional study in long-term survivors of CAYA allo-HSCT combining clinical examinations and patient-reported outcome measures. Results: We included 103 survivors, 55 (53%) females, median age of 19.6 years [range 0.3-29.9] at HSCT, 16.8 years [6.0-32.0] from HSCT, and 77 (75%) with underlying malignancy. Overall, 32 (31%) survivors were diagnosed with active cGVHD. The risk of active cGVHD was increased with prior acute GVHD and reduced with in vivo T cell depletion. cGVHD severity was associated with increased symptom burden, but not with adverse HRQOL. Compared to Norwegian population norms, allo-HSCT survivors reported significantly lower HRQOL. Conclusion: These results indicate a high prevalence of cGVHD in long-term survivors of CAYA allo-HSCT. Although we did not find an association between cGVHD severity and HRQOL, survivors reported significantly poorer HRQOL compared to population norms. Knowledge on the long-term consequences of cGVHD will be important for optimizing treatment and long-term follow-up care after CAYA allo-HSCT.

Feasibility and acceptability of telehealth and contactless delivery of human papillomavirus (HPV) self-testing for cervical screening with Maori and Pacific women in a COVID-19 outbreak in Aotearoa New Zealand.

AIM: To determine the feasibility and acceptability of a telehealth offer and contactless delivery of human papillomavirus (HPV) cervical screening self-test during the 2021 COVID-19 Level 4 lockdown in Auckland, New Zealand. METHODS: A small proof-of-concept study was undertaken to test telehealth approaches in never-screened, due or overdue Maori and Pacific women enrolled in a local Primary Health Organisation (PHO). Study invitation, active follow-up, nurse-led discussions, result notification and a post-test questionnaire were all delivered through telehealth. RESULTS: A sample of 197 eligible Maori and Pacific women were invited to take part, of which 86 women were successfully contacted. Sixty-six agreed to take part. Overall uptake was 61 samples returned (31.8%) and uptake of all contactable women was 70.9%. Six of the 61 HPV self-tests (9.8%) were positive, all for non 16/18 types, and were referred for cytology. Three had negative cytology results, and three with positive cytology results were referred for colposcopy. CONCLUSION: The offer of HPV self-testing during COVID-19 lockdown was both feasible and highly acceptable for Maori and Pacific women. Importantly, HPV self-testing via telehealth and mail-out, alongside other options, offers a potential pro-equity approach for addressing the impact of deferred screens due to COVID-19 and other longstanding coverage issues.

Impaired right ventricular function in long-term survivors of allogeneic haematopoietic stem-cell transplantation.

AIMS: Survivors of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) are at higher risk of cardiovascular disease. We aimed to describe right ventricular (RV) systolic function and risk factors for RV dysfunction in long-term survivors of allo-HSCT performed in their youth. METHODS AND RESULTS: This cohort included 103 survivors (53% female), aged (mean±SD) 17.6±9.5 years at allo-HSCT, with a follow-up time of 17.2±5.5 years. Anthracyclines were used as first-line therapy for 44.7% of the survivors. The RV was evaluated with echocardiography, and found survivors to have reduced RV function in comparison to a group of healthy control subjects: Tricuspid annular plane systolic excursion, (TAPSE, 20.8±3.7 mm vs 24.6±3.8 mm, p<0.001), RV peak systolic velocity (RV-s', 11.2±2.3 cm/s vs 12.3±2.3 cm/s, p=0.001), fractional area change (FAC, 41.0±5.2% vs 42.2±5.1%, p=0.047) and RV free-wall strain (RVFWS, -27.1±4.2% vs -28.5±3.3%, p=0.043). RV systolic dysfunction (RVSD) was diagnosed in 14 (13.6%), and was strongly associated with progressive left ventricular systolic dysfunction (LVSD). High dosages of anthracyclines were associated with greater reductions in RV and LV function. Multivariable linear regressions confirmed global longitudinal strain to be a significant independent predictor for reduced RV function. CONCLUSION: Impaired RV function was found in long-term survivors of allo-HSCT who were treated in their youth. This was associated with progressive left ventricle dysfunction, and pretransplant therapies with anthracyclines. The occurrence of RVSD was less frequent and was milder than coexisting LVSD in this cohort.

Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial.

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden.Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n = 55) or usual care alone (control, n = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder.Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points (P = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group.Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).

The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure.

Objective: Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF. Methods: We analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls. Results: Compared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years. Conclusion: Our findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.

Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study.

PURPOSE: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O2peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function. METHODS: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test. RESULTS: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DLCO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O2peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O2peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O2peak was associated with low DLCO, low LVEF, BOS, overweight, and inactivity. CONCLUSION: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

Kinetic and structure-activity studies of the triazolium ion-catalysed benzoin condensation.

Steady-state kinetic and structure-activity studies of a series of six triazolium-ion pre-catalysts 2a-2f were investigated for the benzoin condensation. These data provide quantitative insight into the role of triazolium N-aryl substitution under synthetically relevant catalytic conditions in a polar solvent environment. Kinetic behaviour was significantly different to that previously reported for a related thiazolium-ion pre-catalyst 1, with the observed levelling of initial rate constants to νmax at high aldehyde concentrations for all triazolium catalysts. Values for νmax for 2a-2f increase with electron withdrawing N-aryl substituents, in agreement with reported optimal synthetic outcomes under catalytic conditions, and vary by 75-fold across the series. The levelling of rate constants supports a change in rate-limiting step and evidence supports the assignment of the Breslow-intermediate forming step to the plateau region. Correlation of νmax reaction data yielded a positive Hammett ρ-value (ρ = +1.66) supporting the build up of electron density adjacent to the triazolium N-Ar in the rate-limiting step favoured by electron withdrawing N-aryl substituents. At lower concentrations of aldehyde, both Breslow-intermediate and benzoin formation are partially rate-limiting.

Summer warming explains widespread but not uniform greening in the Arctic tundra biome.

Arctic warming can influence tundra ecosystem function with consequences for climate feedbacks, wildlife and human communities. Yet ecological change across the Arctic tundra biome remains poorly quantified due to field measurement limitations and reliance on coarse-resolution satellite data. Here, we assess decadal changes in Arctic tundra greenness using time series from the 30 m resolution Landsat satellites. From 1985 to 2016 tundra greenness increased (greening) at ~37.3% of sampling sites and decreased (browning) at ~4.7% of sampling sites. Greening occurred most often at warm sampling sites with increased summer air temperature, soil temperature, and soil moisture, while browning occurred most often at cold sampling sites that cooled and dried. Tundra greenness was positively correlated with graminoid, shrub, and ecosystem productivity measured at field sites. Our results support the hypothesis that summer warming stimulated plant productivity across much, but not all, of the Arctic tundra biome during recent decades.

An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ.

BACKGROUND: AMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2-3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak. METHODS: All records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word "AMB-FUBINACA" was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2. FINDINGS: Sixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from <45 ng/mL to >1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications. INTERPRETATION: This study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ. FUNDING: All work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.

Robust diffraction-limited near-infrared-to-near-ultraviolet wide-field imaging from stratospheric balloon-borne platforms-Super-pressure Balloon-borne Imaging Telescope performance.

At a fraction of the total cost of an equivalent orbital mission, scientific balloon-borne platforms, operating above 99.7% of the Earth's atmosphere, offer attractive, competitive, and effective observational capabilities-namely, space-like seeing, transmission, and backgrounds-which are well suited for modern astronomy and cosmology. The Super-pressure Balloon-borne Imaging Telescope (SUPERBIT) is a diffraction-limited, wide-field, 0.5 m telescope capable of exploiting these observing conditions in order to provide exquisite imaging throughout the near-infrared to near-ultraviolet. It utilizes a robust active stabilization system that has consistently demonstrated a 48 mas 1σ sky-fixed pointing stability over multiple 1 h observations at float. This is achieved by actively tracking compound pendulations via a three-axis gimballed platform, which provides sky-fixed telescope stability at < 500 mas and corrects for field rotation, while employing high-bandwidth tip/tilt optics to remove residual disturbances across the science imaging focal plane. SUPERBIT's performance during the 2019 commissioning flight benefited from a customized high-fidelity science-capable telescope designed with an exceptional thermo- and opto-mechanical stability as well as a tightly constrained static and dynamic coupling between high-rate sensors and telescope optics. At the currently demonstrated level of flight performance, SUPERBIT capabilities now surpass the science requirements for a wide variety of experiments in cosmology, astrophysics, and stellar dynamics.

Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors. OBJECTIVES: The purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood. METHODS: Our cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of <52% in men and <54% in women, and/or a reduced global longitudinal strain (GLS) of ≥-17%. Multivariable linear regression was used to determine independent predictors of 2D-LVEF and GLS. RESULTS: Allo-HSCT survivors had significantly reduced LV systolic function compared with control subjects: 2D-LVEF (55.2 ± 5.8% vs. 59.0 ± 2.9%; p < 0.001), 3D LVEF (54.0 ± 5.1% vs. 57.6 ± 2.7%; p < 0.001), and GLS (-17.5 ± 2.2% vs. -19.8 ± 1.4%; p < 0.001). LVSD was found in 44.2%, of whom 28.3% were symptomatic. Clinical factors independently associated with 2D-LVEF and/or GLS included age, anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension. In the 45% of survivors pre-treated with anthracyclines, the effect of anthracyclines on 2D-LVEF and GLS was dose-dependent. CONCLUSIONS: LVSD is common in long-term survivors of allo-HSCT treated in their youth. Pre-HSCT therapies with anthracyclines, age, heart rate, hypertension, and graft versus host disease are associated with measures of LV function.

Climate change decreases the cooling effect from postfire albedo in boreal North America.

Fire is a primary disturbance in boreal forests and generates both positive and negative climate forcings. The influence of fire on surface albedo is a predominantly negative forcing in boreal forests, and one of the strongest overall, due to increased snow exposure in the winter and spring months. Albedo forcings are spatially and temporally heterogeneous and depend on a variety of factors related to soils, topography, climate, land cover/vegetation type, successional dynamics, time since fire, season, and fire severity. However, how these variables interact to influence albedo is not well understood, and quantifying these relationships and predicting postfire albedo becomes increasingly important as the climate changes and management frameworks evolve to consider climate impacts. Here we developed a MODIS-derived 'blue sky' albedo product and a novel machine learning modeling framework to predict fire-driven changes in albedo under historical and future climate scenarios across boreal North America. Converted to radiative forcing (RF), we estimated that fires generate an annual mean cooling of -1.77 ± 1.35 W/m2 from albedo under historical climate conditions (1971-2000) integrated over 70 years postfire. Increasing postfire albedo along a south-north climatic gradient was offset by a nearly opposite gradient in solar insolation, such that large-scale spatial patterns in RF were minimal. Our models suggest that climate change will lead to decreases in mean annual postfire albedo, and hence a decreasing strength of the negative RF, a trend dominated by decreased snow cover in spring months. Considering the range of future climate scenarios and model uncertainties, we estimate that for fires burning in the current era (2016) the cooling effect from long-term postfire albedo will be reduced by 15%-28% due to climate change.

Catalytic antibody (catabody) platform for age-associated amyloid disease: From Heisenberg's uncertainty principle to the verge of medical interventions.

Quantum mechanics-based design of useful catalytic antibodies (catabodies) failed because of the uncertain structure of the dynamic catalyst-substrate complex. The Catabody Platform emerged from discovery of beneficial germline gene catabodies that hydrolyzed self-proteins by transient covalent pairing of the strong catabody nucleophile with a weak target protein electrophile. Catabodies have evolved by Darwinian natural selection for protection against misfolded self-proteins that threatened survival by causing amyloid disease. Ancient antibody scaffolds upregulate the catalytic activity of the antibody variable (V) domains. Healthy humans universally produce beneficial catabodies specific for at least 3 misfolded self-proteins, transthyretin, amyloid ß peptide and tau protein. Catabody are superior to ordinary antibodies because of catalyst reuse for thousands of target destruction cycles with little or no risk of causing inflammation, a must for non-toxic removal of abundant targets such as amyloids. Library mining with electrophilic target analogs (ETAs) isolates therapy-grade catabodies (fast, specific). Ex vivo- and in vivo-verified catabodies specific for the misfolded protein are available to dissolve brain, cardiac and vertebral amyloids. Immunization with ETAs overcomes important ordinary vaccine limitations (no catabody induction, poor immunogenicity of key target epitopes). We conceive electrophilic longevity vaccines that can induce catabody synthesis for long-lasting protection against amyloid disease.

Single Versus Standard Multiview Assessment of Global Longitudinal Strain for the Diagnosis of Cardiotoxicity During Cancer Therapy.

OBJECTIVES: The goal of this study was to compare echocardiographic measurements of global longitudinal strain (GLS) (using 3 apical views) with single-view longitudinal strain (LS, 4- or 2-chamber [4CV_LS and 2CV_LS, respectively]) for detection of cancer-therapy related cardiotoxicity. BACKGROUND: GLS is useful for the detection of cardiotoxicity, but the need for repeated measurements poses a significant burden on busy echocardiography laboratories. A single-view LS measurement, possibly at point of care, could improve efficiency. METHODS: Seventeen international centers prospectively recruited 108 patients (mean age 54 ± 13 years) at high risk for cardiotoxicity as part of the ongoing SUCCOUR (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy) randomized controlled trial. Echocardiography performed at baseline and follow-up were analyzed in a core laboratory setting blinded to clinical information. Peak systolic GLS and LS were measured from raw data. Cardiotoxicity was defined by reduction in left ventricular ejection fraction >0.10 to <0.55 or a relative drop in GLS by ≥12%. RESULTS: Cardiotoxicity developed in 46 patients by either criteria. Baseline and follow-up 2-dimensional left ventricular ejection fraction were 61 ± 4% and 58 ± 5%, respectively (p < 0.001). The baseline GLS (-20.9 ± 2.4%) was not different from 4CV_LS (-20.7 ± 2.5%; p = 0.09) or 2CV_LS (-21.1 ± 3.1%; p = 0.25). The follow-up GLS (-19.5 ± 2.4%) was also similar to 4CV_LS (-19.5 ± 2.6%; p = 0.80) and 2CV_LS (-19.7 ± 3.1%; p = 0.19). There was good correlation between GLS and 4CV_LS at baseline (r = 0.86; p < 0.001) and follow-up (r = 0.89; p < 0.001) and with 2CV_LS at baseline (r = 0.87; p < 0.001) and follow-up (r = 0.88; p < 0.001). However, there was 15% to 22% disagreement between GLS and 4CV_LS or 2CV_LS for the detection of cardiotoxicity. The interobserver and intraobserver reproducibility was higher for GLS (intraclass correlation: 0.93 to 0.95; coefficient of variance: 2.9% to 3.7%) compared with either single-chamber-based LS measurement (intraclass correlation: 0.85 to 0.91; coefficient of variance: 4.1% to 4.8%). CONCLUSIONS: Although there was good correlation between GLS and single-view LS measurements, single-view LS measurement led to disagreement in the diagnosis of cardiotoxicity in up to 22% of patients. GLS measurements were more reproducible than single-view LS. GLS based on 3 apical views should remain the preferred technique for detection of cardiotoxicity. (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy [SUCCOUR]; ACTRN12614000341628).

Cosmology and fundamental physics with the Euclid satellite.

Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.

Semiautomated biventricular segmentation in three-dimensional echocardiography by coupled deformable surfaces.

With the advancement of three-dimensional (3-D) real-time echocardiography in recent years, automatic creation of patient specific geometric models is becoming feasible and important in clinical decision making. However, the vast majority of echocardiographic segmentation methods presented in the literature focus on the left ventricle (LV) endocardial border, leaving segmentation of the right ventricle (RV) a largely unexplored problem, despite the increasing recognition of the RV's role in cardiovascular disease. We present a method for coupled segmentation of the endo- and epicardial borders of both the LV and RV in 3-D ultrasound images. To solve the segmentation problem, we propose an extension of a successful state-estimation segmentation framework with a geometrical representation of coupled surfaces, as well as the introduction of myocardial incompressibility to regularize the segmentation. The method was validated against manual measurements and segmentations in images of 16 patients. Mean absolute distances of [Formula: see text], [Formula: see text], and [Formula: see text] between the proposed and reference segmentations were observed for the LV endocardium, RV endocardium, and LV epicardium surfaces, respectively. The method was computationally efficient, with a computation time of [Formula: see text].